# Managing Bone Infections Beyond Systemic Antibiotics: A Scoping Review

## TL;DR

This paper reviews alternative and adjunctive treatments for bone infections beyond traditional systemic antibiotics, focusing on local delivery systems and immunomodulatory strategies.

## Contribution

The paper provides a comprehensive scoping review of emerging therapeutic approaches for managing bone infections.

## Key findings

- Local antibiotic delivery systems can achieve high antimicrobial concentrations at the infection site with minimal systemic exposure.
- Immunomodulatory strategies like stem cell therapies and bacteriophages show promise in improving infection control and bone regeneration.
- Personalized approaches using biomarkers and AI are advancing diagnosis and treatment of bone infections.

## Abstract

Bone infections, including osteomyelitis, prosthetic joint infections, and fracture-related infections, represent a persistent and growing clinical problem associated with substantial morbidity, mortality, and healthcare costs. Their management is complicated by limited bone vascularization, biofilm formation, intracellular bacterial persistence, dysregulated host immune responses and reduced antibiotic delivery to the infection site, which promote chronic infection and recurrence. The limitations of conventional treatment strategies based on surgical debridement and prolonged systemic antibiotic therapy, together with their association with antimicrobial resistance and systemic toxicity, have led to growing interest in alternative and adjunctive therapeutic approaches. Local antibiotic delivery systems, such as polymethyl methacrylate, calcium sulfate, hydroxyapatite-based composites, hydrogels, antibiotic-impregnated bone grafts, and nanoparticle carriers, enable high local antimicrobial concentrations while minimizing systemic exposure. From a different therapeutic perspective, immunomodulatory strategies, including mesenchymal stem cell-based therapies, cytokine-targeted interventions, bacteriophages, quorum-sensing inhibitors, and non-antibiotic antimicrobials, represent emerging approaches aimed at improving infection control and supporting bone regeneration. Advances in biomarker profiling, molecular diagnostics, and artificial intelligence-assisted analyses further support personalized approaches to diagnosis, monitoring, and treatment. Despite encouraging early results, clinical translation remains limited by methodological and regulatory challenges, underscoring the need for integrated, innovative treatment strategies.